Tohoku University Hospital

Studies investigating growth impairment (GI) in children with intestinal failure (IF) have seldom reported its associated factors. We hypothesized that a deficient nutritional intake would affect GI in children with IF. Nineteen patients (2-16 years old) who underwent home-based parenteral nutrition (PN) management at our institution, were divided into patients with or without GI (GI+/GI-). GI was defined as a height-for-age z-score (HAZ) ≤ -2. We performed between-group comparisons of HAZ in the intestinal rehabilitation program (IRP)/nutrition support team (NST) introduction time, PN dependency, residual small intestine length (RSIL), nutritional intake (calorie, protein, lipids, and carbohydrates), caloric intake ratio, and nutrient intake as a percentage of the recommended intake. Six patients were in the GI+ group. PN dependency was significantly higher in the GI+ group (GI+, 109.8 %; GI < median, 61.7 %, P = 0.036). RSIL did not differ significantly between the groups (50 cm vs. 45 cm, P = 0.879). In the GI+ group, the caloric percentage of lipids was significantly lower (11.9 % vs. 17.5 %, P = 0.002), but that for carbohydrates was significantly higher (76.8 % vs. 66.8 %, P = 0.002), while lipid sufficiency was significantly lower (37.5 % vs. 89.6 %, respectively; P < 0.001). Protein intake in the GI+ group was significantly lower; however, the corresponding sufficiency was > 100 % in both groups (136.5 % vs. 209.2 %, P = 0.005). For children with IF, a low intake ratio of proteins and lipids relative to energy requirement and required nutrient levels may inhibit adequate growth.

Convexity germ cell tumors are exceedingly rare and may closely mimic meningiomas, particularly in young men. This case report presents a rare convexity germ cell tumor characterized by dural invasion and skull destruction. An 18-year-old man presented with headache and nausea. Neuroimaging demonstrated a right frontoparietal extra-axial mass accompanied by adjacent skull hyperostosis and significant cerebral edema. Based on these radiological findings, a convexity meningioma was strongly suspected, and a craniotomy was performed for tumor resection. Unexpectedly, histopathological examination revealed a germ cell tumor with diffuse infiltration of the dura and bone, characterized by a high Ki-67 labeling index and immunoreactivity for placental alkaline phosphatase. Subsequent systemic evaluation identified a mass in the anterior mediastinum, leading to a final diagnosis of intracranial metastasis from a primary mediastinal seminoma. The patient was referred for systemic chemotherapy and achieved a complete response. Germ cell tumorscannot be excluded in young male patients, even when lesions arise on the convexity and exhibit imaging features typical of meningiomas. Accordingly, germ cell tumors should be included in the differential diagnosis, and tumor marker evaluation and nuclear medicine studies should be proactively performed.

BackgroundA Japanese phase 2 trial of encorafenib plus binimetinib met the primary endpoint of the centrally assessed objective response rate in patients with unresectable BRAF V600E-mutated thyroid cancer. Consequently, encorafenib plus binimetinib has been approved in Japan. We present the health-related quality of life (HR-QoL) outcomes from the trial.MethodsThe multicenter, open-label, uncontrolled phase 2 trial enrolled patients with unresectable locally advanced or metastatic BRAF V600E-mutated thyroid cancer. HR-QoL score, one of the secondary endpoints, was assessed using the EORTC QLQ-C30 and QLQ-THY34 at baseline and during follow-up. The minimal important change (MIC) threshold was set at 10 points.ResultsWe enrolled 22 patients with BRAF V600E-mutated thyroid cancer. The median follow-up was 11.5 months. Completion rates for the questionnaires were 100% (22 of 22 patients) at baseline and 68% (15 of 22) at week 20. Until week 20, changes from baseline were below MIC at most time points in 29 of all 32 domains in QLQ-C30 and QLQ-THY34. In the other 3 domains, patients showed tendencies toward improvement (social support and appetite loss) or deterioration (joint pain) for consecutive time points. Patients with anaplastic thyroid cancer showed tendencies toward improvement for swallowing, restlessness, body image, and discomfort in the head and neck, from the first assessment after the initial treatment.ConclusionThe combination therapy of encorafenib plus binimetinib for unresectable BRAF V600E-mutated thyroid cancer was associated with generally maintained HR-QoL. Considering the efficacy and safety data from the trial, the regimen may provide clinical benefits while maintaining HR-QoL.

This study aimed to evaluate the risk of major congenital malformations (MCMs) associated with first-trimester exposure to antipsychotics, using a large claims database in Japan. This retrospective cohort study was based on data from a large claims database in Japan. We used a large claims database from 2010 to 2019. Dates of pregnancy onset and delivery were estimated using the developed algorithms. Overall MCMs were defined according to the International Classification of Diseases, 10th revision codes. To address confounding by indication, the risk of MCM in relation to first-trimester antipsychotic use was evaluated among pregnant women with psychiatric disorders diagnosed before the end of the first-trimester. We compared the prevalence of MCMs among infants born to pregnant women with or without first-trimester exposure to antipsychotics and estimated the weighted odds ratios (wORs) using propensity-score overlap weights. The prevalence of psychiatric diagnoses before the end of the first-trimester was 6291 women among the 91 390 who delivered between 2010 and 2019. Among the 6291 diagnosed with psychiatric disorders, 317 were exposed to any antipsychotics during the first-trimester of pregnancy. The prevalence of overall MCMs among live births was 411 (6.9%) among women unexposed to any antipsychotics and 24 (7.6%) among those exposed. The first-trimester exposure to any antipsychotics was not significantly associated with overall MCMs when wORs were calculated using propensity-score overlap weights (wOR 1.144, 95% confidence intervals 0.727-1.799). Exposure to any antipsychotics during the first-trimester of pregnancy was not associated with an increased risk of overall MCMs in infants.

Glucocorticoids (GC) comprise a cornerstone in the treatment of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV); however, prolonged GC exposure leads to substantial toxicity and immune system-related complications. Hence, identifying treatment strategies that enable early GC withdrawal while maintaining disease control is of clinical importance. To investigate the proportion and characteristics of patients achieving GC-free clinical remission (GFCR) 48 weeks after treatment initiation in patients with newly diagnosed microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) and examine their long-term clinical outcomes (up to week 96). We conducted a retrospective cohort study using clinical data from a multicenter, nationwide registry in Japan comprising patients with newly diagnosed MPA or GPA and at least 48 weeks of follow-up. GFCR was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 with complete GC withdrawal. Univariable and multivariable logistic regression analyses were used to identify independent predictors of GFCR at week 48, and a sensitivity analysis using a matched cohort was performed to validate robustness. A total of 728 patients were enrolled in the registry, of whom 544 were followed for ≥ 48 weeks; among them, 29 (5.3%) achieved GFCR at week 48. Use of rituximab (RTX) for induction therapy and avacopan within 48 weeks were independently associated with achieving GFCR (multivariable analysis, model 1: RTX: odds ratio [OR]: 3.9, 95% confidence interval [CI]: 1.5–10.0; avacopan: OR: 24.3, 95% CI: 5.8–101.9; both p < 0.01). Conversely, methylprednisolone pulse therapy was associated with a lower likelihood of achieving GFCR (multivariable analysis, model 1: OR: 0.08, 95% CI: 0.02–0.44; p < 0.01). Patient’s demographic and baseline disease characteristics were not predictive of GFCR. In the long-term (weeks 48 through 96), the rates of death, relapse, and serious infection were similar regardless of GFCR status at week 48. The use of RTX for induction therapy and avacopan within 48 weeks is independently associated with achieving GFCR at week 48 in patients with MPA and GPA, supporting their potential as key components of GC-sparing strategies in AAV. Prospective studies are needed to confirm these results and optimize treatment algorithms to ensure disease control and minimize GC-related toxicity.

Metastatic colorectal cancer (mCRC) differs clinically based on RAS and BRAF mutations or DNA methylation. However, in mCRC, the prognostic value and biological characteristics of genome-wide DNA methylation status (GWMS) in each RAS/BRAF genotype is unknown. To clarify this, primary tumor samples from patients with informed consent in the phase III TRICOLORE study were collected, and RAS and BRAF mutations, immunohistochemical staining of mismatch repair-related proteins, comprehensive gene expression, and genome-wide DNA methylation were analyzed. The tumor samples were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC). Gene set enrichment analysis (GSEA) was conducted using microarray data. A total of 226 patients were included and classified into the RAS/BRAF wild-type (wt) (n = 125), RAS mutant (mt) (n = 87), and BRAF mt (n = 14), of whom 22 (17.6%), 30 (34.5%), and 14 (100%) had HMCC. HMCC exhibited significantly worse overall survival (OS) than that of LMCC in the RAS/BRAF wt group but not in the RAS mt group. In GSEA, RAS/BRAF wt HMCC was associated with microsatellite instability and BRAF V600E mutation. The poor prognosis of RAS/BRAF wt HMCC may be attributed to gene expression patterns associated with microsatellite instability and BRAF V600E mutation.

The association between blood pressure (BP) and the mortality risk may vary depending on the comorbidities. This study was conducted to investigate the subgroup-specific correlation between systolic BP (SBP) and mortality in patients with coronary artery disease undergoing percutaneous coronary intervention (PCI). The Clinical Deep Data Accumulation System for PCI (CLIDAS-PCI), a nation-wide multicenter database with seven tertiary medical hospitals in Japan, retrospectively collected data on patients undergoing PCI for acute coronary syndrome or stable coronary artery disease. Cubic spline curves modeled the relationship between SBP and all-cause death in the entire cohort and subgroups stratified by age, sex, diabetes, left ventricular (LV) hypertrophy, renal function and LV systolic function. We assessed the SBP, which minimizes mortality risk. A total of 8384 patients [71 [IQR 64, 78] years, 6494 (77%) male] with SBP at hospital discharge were analyzed. During 2.7 years of median follow-up, 695 deaths occurred. In the overall population, spline analysis demonstrated a nadir range of mortality risk around an SBP of 110-130 mmHg. Subgroup analyses revealed that elderly (age ≥ 80 years), those with renal dysfunction, and those with preserved LV systolic function had higher SBP levels associated with lowest risk. Conversely, patients <80 years, those with better renal function, and those with LV systolic dysfunction exhibited lower SBP levels at lowest risk. This study demonstrated differential association between SBP and mortality risk in various subgroups, highlighting the need for personalized BP management in multimorbid patients with coronary artery disease.

Background Long-term endocrine therapy for breast cancer often causes menopause-like symptoms, affecting quality of life. Although Japanese traditional (Kampo) medicine is utilized for relief, research remains limited. Objective This retrospective observational study aimed to evaluate the efficacy of Kampo medicines in managing endocrine therapy-related side effects in breast cancer patients. Methods Data from breast cancer patients receiving endocrine therapy treated with Kampo medicines at Japanese Red Cross Ishinomaki Hospital between July 2017 to June 2024 were analyzed. Symptom severity was measured using a Numerical Rating Scale (NRS; 0–10). Kampo medicine, administered by a specialist, was tailored to individual symptoms and physical findings. Multivariate analysis was performed to examine the association between symptom relief. Symptom progression was analyzed using Kaplan-Meier curves, and outcomes were compared using the log-rank test. Results Fifty-three patients (median age: 54) were enrolled. Vasomotor, motor/sensory, and psychiatric symptoms accounted for 90% of complaints. After 6 months, 75% of patients reported NRS scores of 3 or less (enabling them to perform daily activities without difficulty). Keishibukuryogan (KBG) or keishibukuryogankayokuinin (KBGY) were the most prescribed (41.5%). Multivariate analysis indicated KBG/KBGY was significantly associated with symptom relief (Hazard Ratio 4.18; 95% CI 1.03–16.92; p = 0.046). Patients prescribed KBG/KBGY experienced significantly faster overall symptom improvement than those on other Kampo medicines ( p = 0.022). Conclusion Kampo medicines are effective in alleviating side effects in breast cancer patients undergoing endocrine therapy. KBG/KBGY has shown promise in reducing overall symptoms.

In rehabilitation research, machine learning (ML) algorithms are being increasingly applied to predict the ability of patients with stroke and other acquired brain injuries to perform activities of daily living (ADL). However, many previous studies have relied on complex data, such as imaging or blood tests, which require advanced equipment and specialized expertise and are difficult to apply in general clinical settings. We aimed to predict ADL independence in patients with stroke and other acquired brain injuries at the start of rehabilitation using routine assessment data. This retrospective study involved 379 patients with stroke or other acquired brain injuries who received rehabilitation at our hospital between September 2008 and August 2022. Three ML models - support vector machine (SVM), random forest (RF), and Light Gradient-Boosting Machine (LightGBM) - were used to classify Functional Independence Measure scores. Predictors included age, sex, Japan Coma Scale score, and Brunnstrom recovery stage. All models performed above chance, with SVM achieving the highest F1 score (0.862), followed by RF (0.857) and LightGBM (0.838). Analysis of variance revealed a significant effect of the classifier on performance (P < .001), with SVM and RF significantly outperforming LightGBM. SHapley Additive exPlanations analysis identified lower- and upper-limb Brunnstrom recovery stage, impaired consciousness, and age as key predictive features. ML algorithms can accurately predict ADL independence using initial rehabilitation assessment data without reliance on advanced medical technologies. The use of these algorithms may enhance clinical decision-making, and they may be particularly valuable in resource-limited settings.